title: p53 regulates glucose metabolism by miR-34a.
abstract: Cancer cells rely mainly on glycolysis rather than mitochondrial respiration for energy production, which is called the Warburg effect. p53 mutations are observed in about half of cancer cases, and p53 controls the cell cycle and cell death in response to cellular stressors. p53 has been emphasized as a metabolic regulator involved in glucose, glutamine, and purine metabolism. Here, we demonstrated metabolic changes in cancer that occurred through p53. We found that p53-inducible microRNA-34a (miR-34a) repressed glycolytic enzymes (hexokinase 1, hexokinase 2, glucose-6-phosphate isomerase), and pyruvate dehydrogenase kinase 1. Treatment with an anti-miR-34a inhibitor relieved the decreased expression in these enzymes following DNA damage. miR-34a-mediated inhibition of these enzymes resulted in repressed glycolysis and enhanced mitochondrial respiration. The results suggest that p53 has a miR-34a-dependent integrated mechanism to regulate glucose metabolism.
authors.affiliation: National Creative Research Center for Epigenome Reprogramming Network, Departments of Biomedical Sciences and Biochemistry and Molecular Biology, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: Hwa-Ryeon
authors.initials: HR
authors.lastname: Kim
authors.forename: Jae-Seok
authors.initials: JS
authors.lastname: Roe
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Cho
authors.forename: Hong-Duk
authors.initials: HD
authors.lastname: Youn
mesh_terms: D005947:Glucose / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53; D005947:Glucose
keywords: GPI; Glycolysis; HK; PDK1; miR-34a; p53